For example, selected lines of mice produced from breeding animals for certain endophenotypes have been widely used in mapping quantitative trait loci (QTL), an analytical method utilized to identify

regions of the genome influencing a specific trait by comparing genetic markers that are shared by lines or strains displaying extremes in quantitative endophenotypes. Several selected lines that differ with respect to various alcohol-related traits have been developed to identify genetic differences contributing to differences in the effects of Inhibitors,research,lifescience,medical alcohol. This area of research has recently been reviewed.10 Although animal models provide for “proof of concept,” which indicates that the definition and utilization of endophenotypes can lead to a better understanding of the etiology of the endophenotype and provide a means for identifying which genetic factors Inhibitors,research,lifescience,medical would be of interest to study in humans, not all observations in the nonhuman animal are necessarily applicable to humans. Thus, it is essential to conduct studies with human populations in order to elucidate the pathophysiology

of human disease. Recent research efforts with humans have focused on the identification and incorporation of endophenotypes to study risk factors for alcoholism. Schuckit recently proposed that the majority of genetically related markers of alcoholism risk were Inhibitors,research,lifescience,medical represented by five relatively independent overarching categories (endophenotypes), which include level of response, neuronal or behavioral disinhibition, independent axis I major psychiatric disorders, the opioid system, and alcohol-metabolizing enzymes.11 A variety of additional traits have been investigated in epidemiological Inhibitors,research,lifescience,medical research as potential endophenotypes for alcohol dependence. These include endophenotypes related to endocrine measures, electrophysiology, personality, and drinking behavior. Behavioral and physiological traits Low alcohol response Researchers have investigated the significance of sensitivity to intoxication with respect to the development Inhibitors,research,lifescience,medical of alcohol dependence.12-15 Low response to alcohol is a wellcharacterized biological measure, which is indicative of

alcohol sensitivity, Parvulin specifically the need for more alcohol to produce an effect.11 It has been hypothesized that low response increases the risk of alcohol dependence by increasing the probability of heavy drinking and acquisition of tolerance and dependence.11 Historically, level of response (ie, a low response) has been assessed through various measurements, which include level of change in subjective feelings of intoxication, motor performance, hormone Protein Tyrosine Kinase inhibitor levels, and/or electrophysiological measures observed at specific blood alcohol concentrations, or by a self-report of the number of drinks required for specific effects.16-18 The effects of ethanol can be measured by the use of the alcohol challenge test, where subjects are typically given three to five standard drinks to be consumed over approximately 10 minutes.